Developmental expression of Sp1 in the mouse.

Abstract

The expression of the trans-acting transcription factor Spl in mice was defined by a combination of RNA analysis and immunohistochemical localization of the Spl protein. Although ubiquitously expressed, there was an unexpected difference of at least 100-fold in the amount of Spl message in different cell types. Spl protein levels showed corresponding marked differences. Substantial variations in Spl expression were also found in some cell types at different stages of development. Spl levels appeared to be highest in developing hematopoietic cells, fetal cells, and spermatids, suggesting that an elevated Spl level is associated with the differentiation process. These results indicate that Spl has a regulatory function in addition to its general role in the transcription of housekeeping genes.The control of transcription is a key step in the regulation of gene expression. Although specific DNA elements around and within a gene contain the information directing this regulation, proteins that recognize these DNA sequences are the factors actually responsible for modulating RNA polymerase activity. Several sequence-specific DNA-binding transcription factors that are involved in the process of transcriptional regulation have been described, and much has been learned at the molecular level about their structure and function (24,25). Some transcription factors are characterized by cell type-specific expression and are involved in regulating the specialized functions of that cell. For example, the Oct-2 protein is B cell specific (5, 30), and Myo Dl is muscle cell specific (7). In contrast, other factors appear to be ubiquitously expressed and involved in the transcription of genes expressed in all cell types. A well-characterized example of this type of factor is Spl, which is reportedly found in all mammalian cell nuclei (2).Although originally described as a specific factor required for simian virus 40 (SV40) transcription (9, 10), Spl interacts with GC boxes in the promoters of many other genes. For example, cellular genes that contain one or more GC boxes include adenosine deaminase (33), hypoxanthine guanine phosphoribosyl transferase (23) binding sites will require larger amounts of Spl than are required for genes with strong binding sites. Thus, some genes will be more sensitive than others to variations in the level of Spl. Third, the observation that Spl levels increase during SV40 infection (15, 28) implies that Spl levels can be regulated. In this system, alteration of the normal Spl expression may support the SV40 viral life cycle and the accompanying cellular changes.To further investigate the regulation and action of Spl, we have determined Spl expression in different cell types during development of the mouse. In this paper, we show that although Spl is ubiquitously expressed, substantial variations that are likely to play an important regulatory role occur in Spl expression. These studies are relevant to defining (i) the physiological role of Spl in growth and development, (ii) the variations in expressi...

Hypermethylated promoter region of DR3, the death receptor 3 gene, in rheumatoid arthritis synovial cells

“…Several transcription factors, such as GATA, Oct-1, or Sp1, can bind the CpG island. In particular, Sp1 is a ubiquitously expressed zinc-finger transcription factor that supports mRNA expression in a variety of eukaryotic genes that lack the functional TATA box (17,18). Among Sp family proteins, Sp1 and Sp3 were shown to be ubiquitously expressed in human tissues, and transcriptional activity enhanced by Sp1 was shown to be suppressed by Sp3 (32).…”

“…DR-3 is a member of the apoptosis-inducing tumor necrosis factor (TNF) receptor superfamily that includes Fas (12)(13)(14)(15)(16), and its promoter region near the translation start site contains GATA, Oct-1, and two Sp1 binding sites, but without containing either the TATA or the CAAT box. Sp1 is a ubiquitously expressed zinc-finger transcription factor that supports messenger RNA (mRNA) expression in a variety of eukaryotic genes that lack a functional TATA box (17,18), and this may be important for synovial cell activation.…”

Characterization of the mouse dynamin I gene promoter and identification of sequences that direct expression in neuronal cells

“…However, the promoter activity of dynamin I, which seems to be strongly dependent on the ubiquitously expressed Sp1 and NEBP, might be regulated in a tissue-specific manner by these factors in several ways. The first possibility is the availability of these factors ; Saffer et al [41] showed that the levels of Sp1 protein vary between different tissues. They showed that Sp1 expression varies greatly in different cell types and that changes in Sp1 levels occur during development.…”

Oxidative stress and superoxide dismutase in development, aging and gene regulation

“…In the bovine SOD-2 gene the Spl sites have been shown to be necessary for basal promoter function, but not sufficient for conferring responsiveness to lipopotysaccharide. Furthermore, the Spl transcription factor has been shown to be regulated developmentally (264). It is, for example, known that Spl sites regulate the developmental expresssion of both the mouse secretory protease inhibitor p12 (265) and the murine deaminase gene (266).…”